Shinichiro Doi

Preprocedural High-Sensitivity C-Reactive Protein Predicts Long-Term Outcome of Percutaneous Coronary Intervention

BACKGROUND High-sensitivity C-reactive protein (hs-CRP) has been used to predict the risk of adverse cardiac events in patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). Less is known, however, about the association between hs-CRP and long-term outcome after PCI in the Japanese population.Methods and Results:We studied 3,039 all-comer patients with CAD who underwent their first PCI and had data available for preprocedural hs-CRP at Juntendo University between 2000 and 2011. Patients were assigned to tertiles based on preprocedural hs-CRP concentration. We evaluated the incidence of major adverse cardiac events (MACE) including all-cause death, acute coronary syndrome (ACS), and target vessel revascularization (TVR). Patients with higher hs-CRP had a higher prevalence of current smoking, chronic kidney disease and ACS, and a lower prevalence of statin use. During a median follow-up period of 6.5 years, ongoing divergence in MACE with hs-CRP tertile was noted on Kaplan-Meier curves (hs-CRP <0.08 mg/L, 26.4%; 0.08-0.25 mg/L, 38.2%; >0.25 mg/L, 45.6%; log-rank P<0.001). After adjustment for established cardiovascular risk factors, hs-CRP was associated with higher incidence of MACE (hazard ratio [HR], 1.10; 95% CI: 1.04-1.16, P<0.001) and higher all-cause mortality (HR, 1.14; 95% CI: 1.06-1.22, P<0.001). CONCLUSIONS Preprocedural hs-CRP measurement is clinically useful for long-term risk assessment in Japanese patients with established CAD and undergoing PCI.

Impact of preprocedural high-sensitive C-reactive protein levels on long-term clinical outcomes of patients with stable coronary artery disease and chronic kidney disease who were treated with drug-eluting stents

BACKGROUND To evaluate the prognostic impact of preprocedural high-sensitivity C-reactive protein (hsCRP) levels on the long-term clinical outcomes after first-generation drug-eluting stent (DES) implantation in chronic kidney disease (CKD) patients with stable coronary artery disease (CAD). METHODS AND RESULTS We found significant interaction between CKD and hsCRP levels (p=0.0138) in 1176 consecutive patients with stable CAD who were treated with first-generation DES implantation between 2004 and 2009 at our institution. Therefore, we separately analyzed data from patients with and without CKD who were assigned to tertiles based on preprocedural hsCRP levels. We evaluated the incidence of major adverse cardiovascular events (MACE) comprising all-cause death, nonfatal myocardial infarction, and target vessel revascularization after percutaneous coronary intervention during a median follow-up period of 1266 days. The rate of MACE significantly differed among the tertiles (log-rank p=0.0074) in the group with CKD. Multivariate Cox regression analysis significantly associated a higher hsCRP tertile with MACE in the CKD group (hazard ratio 2.39, 95% confidence interval 1.27-4.75, p=0.0062). CONCLUSION Elevated preprocedural serum hsCRP levels might be associated with the long-term clinical outcomes of patients with stable CAD and CKD who were implanted with first-generation DES.

Independent and Combined Effects of Serum Albumin and C-Reactive Protein on Long-Term Outcomes of Patients Undergoing Percutaneous Coronary Intervention

BACKGROUND Both inflammation and malnutrition have been reported to be closely linked to atherosclerosis, especially in patients with chronic kidney disease (CKD). The combined effects of serum albumin and C-reactive protein (CRP) on clinical outcomes after percutaneous coronary intervention (PCI) were investigated.Methods and Results:A total of 2,164 all-comer patients with coronary artery disease who underwent their first PCI and had data available for preprocedural serum albumin and hs-CRP levels between 2000 and 2011 were studied. Patients were assigned to 4 groups according to their median serum albumin and CRP levels (4.1 g/dL and 0.10 mg/dL, respectively). The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction (MI), was evaluated. During a median follow-up period of 7.5 years, 331 cases of MACE (15.3%), including 270 deaths and 61 non-fatal MIs, occurred. Kaplan-Meier curves showed that the rates of MACE differed significantly among the groups (log-rank P<0.0001), even stratified by with or without CKD (both log-rank P<0.0001). After adjustment for established cardiovascular risk factors, low serum albumin with high CRP levels was associated with adverse cardiac events (hazard ratio 2.55, 95% confidence interval 1.72-3,88, P<0.0001, high albumin/low CRP group as reference). CONCLUSIONS The presence of both low serum albumin and high CRP levels conferred a synergistic adverse effect on the risk for long-term MACE in patients undergoing PCI.

Temporal Trends in Clinical Outcomes Following Percutaneous Coronary Intervention in Patients with Renal Insufficiency.

Aim: Renal insufficiency is associated with worse clinical outcomes in patients with coronary artery disease. Since the introduction of percutaneous coronary intervention (PCI), the revascularization therapy has evolved with advances of devices, improvements in operator techniques, and the establishment of medical therapy. We examined temporal trends of the clinical outcomes following PCI in patients with renal insufficiency. Methods: Patients with renal insufficiency after PCI at Juntendo University across three eras (plain balloon angioplasty, bare metal stent (BMS), and drug-eluting stent (DES)) were examined in this study. The primary endpoint was a composite of all-cause mortality, nonfatal acute coronary syndrome, nonfatal stroke, and repeat revascularization within 3-years after the index revascularization. Results: A total of 1,420 patients were examined. Baseline characteristics have become unfavorable over time, whereas administration rate of medications for secondary prevention has increased. The event-free survival rates for the endpoint were different among the groups. Adjusted relative risk reduction for the endpoint was 35% and 51% in the BMS and DES eras (using the plain angioplasty era as reference). The adjusted relative risk reduction of the DES era was 26% compared with that of the BMS era. Conclusions: The incidence of cardiovascular events after PCI has reduced during the 26-year period mainly because of the reduction in repeat revascularization in patients with renal insufficiency, despite the higher risk profiles in the recent era.

Relationship between the prognostic nutritional index and long-term clinical outcomes in patients with stable coronary artery disease

BACKGROUND Malnutrition has recently been reported to correlate with prognosis in patients with heart failure. However, the prognostic significance of nutritional status in patients with stable coronary artery disease (CAD) is unknown. The present study sought to examine the association between nutritional status assessed by the prognostic nutritional index (PNI) and cardiovascular outcomes in patients with stable CAD. METHODS A total of 1988 patients with stable CAD who underwent elective percutaneous coronary intervention (PCI) between 2000 and 2011 were examined. The PNI was calculated as 10×serum albumin (g/dL)+0.005×total lymphocyte count (per mm3). Patients were assigned to tertiles based on their PNI. The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, was evaluated. RESULTS The median PNI was 48.9 (interquartile range: 45.5-52.1). During the median follow-up of 7.5 years, Kaplan-Meier analysis showed that patients with lower PNI tertiles had higher rates of MACE (PNI <46.7: 35.5%; 46.7-50.8: 22.3%; >50.8: 16.0%; log-rank p<0.0001). After adjusting for other risk factors, the PNI was independently associated with MACE (hazard ratio 2.05 per 10 PNI decrease, 95% confidence interval: 1.66-2.54, p<0.0001). Adding the PNI to a baseline model with established risk factors improved the C-index (p=0.03), net reclassification improvement (p=0.03), and integrated discrimination improvement (p=0.0001). CONCLUSIONS The PNI was significantly associated with long-term cardiovascular outcomes in patients with stable CAD. Assessing PNI may be useful for risk stratification of CAD patients undergoing elective PCI.

Clinical impact of high-sensitivity C-reactive protein during follow-up on long-term adverse clinical outcomes in patients with coronary artery disease treated with percutaneous coronary intervention

INTRODUCTION C-reactive protein (CRP) is an established marker for vascular inflammation and predictor of adverse cardiovascular events, but the prognostic value of preprocedural CRP in coronary artery disease (CAD) patients who have undergone percutaneous coronary intervention (PCI) remains controversial. Furthermore, the impact of CRP levels during follow-up in CAD patients after PCI on long-term adverse clinical outcomes is uncertain. We evaluated the association between high-sensitivity (hs)-CRP values at follow-up angiography and long-term clinical outcomes in CAD patients after coronary intervention. METHODS We prospectively enrolled 3507 consecutive CAD patients who underwent first PCI between 1997 and 2011 at our institution. We identified 2509 patients (71.5%) who underwent follow-up angiography (6-8 months after PCI). Of those, 1605 patients (45.8%) who had data available for hs-CRP at follow-up angiography were stratified into three groups according to tertiles of hs-CRP level at the time of follow-up angiography. The primary endpoint was composite of all-cause death and non-fatal acute coronary syndrome (ACS). RESULTS Median follow-up was 1716 days. The cumulative incidence of all-cause death and ACS differed significantly among groups (log-rank, p=0.0002). Multivariate Cox regression analysis showed that a higher hs-CRP level at follow-up angiography was associated with a greater risk of all-cause death and ACS [adjusted hazard ratio (HR) for all-cause death and ACS 2.14, 95% confidence interval (CI) 1.43-3.27, p=0.0002. CONCLUSION Elevated hs-CRP levels during follow-up were significantly associated with higher frequencies of adverse long-term clinical outcomes in patients with CAD after PCI.

CPAP effects on atherosclerotic plaques in patients with sleep-disordered breathing and coronary artery disease: The ENTERPRISE trial

BACKGROUND Sleep-disordered breathing (SDB) is a novel cardiovascular risk factor. To date, the effects of continuous positive airway pressure (CPAP) on coronary plaque atheroma in SDB patients with coronary artery disease (CAD) have remained unclear. The CPAP Effects on Atherosclerotic Plaques in Patients with Sleep-Disordered Breathing and Coronary Artery Disease (ENTERPRISE) trial was designed to evaluate the effects of CPAP treatment in addition to optimal medical treatment on coronary plaque regression in SDB patients. METHODS This study is planned as a prospective, randomized, open-label, single-center study. The presence of SDB is defined as a 3% oxygen desaturation index (ODI) of ≥15 events/h as measured by nocturnal pulse oximetry. A total of 100 eligible SDB patients undergoing intravascular ultrasound (IVUS)-guided percutaneous coronary intervention will be randomly assigned to either CPAP as add-on therapy or no CPAP for SDB (1:1 ratio for CPAP vs. no CPAP). The intervention will consist of 12 months of CPAP treatment. The primary endpoint will be percentage changes in plaque atheroma volume of the non-culprit lesion segment as measured by IVUS. A specialist sleep cardiology team will carefully monitor patients receiving CPAP treatment in order to quickly detect and resolve problems, and to motivate patients to continue treatment. CONCLUSION This study will provide novel information on the effects of SDB and its treatment with CPAP on coronary plaque stability with regard to secondary prevention of CAD.

A novel and simply calculated nutritional index serves as a useful prognostic indicator in patients with coronary artery disease

OBJECTIVE No nutritional index has been firmly established yet in patients with coronary artery disease (CAD). In this study, we propose a simple to calculate nutritional indicator in patients who underwent percutaneous coronary intervention (PCI) by using parameters routinely measured in CAD and evaluated its prognostic implication. METHODS This study is a retrospective observational analysis of a prospective database. The subjects were consecutive 3567 patients underwent their first PCI between 2000 and 2013 at Juntendo University Hospital in Tokyo. The median of the follow-up period was 6.3 years (range: 0-13.6 years). The novel nutritional index was calculated by the formula; Triglycerides (TG) × Total Cholesterol (TC) × Body Weight (BW) Index (TCBI) = TG × TC × BW / 1000 (TG and TC: mg/dl, and BW: kg). RESULTS The Spearman non-parametric correlation coefficient between TCBI and the most often used conventional nutritional index, Geriatric Nutritional Risk Index (GNRI), was 0.355, indicating modest correlation. Moreover, Unadjusted Kaplan-Meier analysis showed higher all-cause mortality, cardiovascular mortality, and cancer mortality in patients with low TCBI. Consistently, elevation of TCBI was associated with reduced all-cause (hazard ratio: 0.86, 95%CI: 0.77-0.96, p < 0.001), cardiovascular (0.78, 0.66-0.92, p = 0.003), and cancer mortality (0.76, 0.58-0.99, p = 0.041) in patients after PCI by multivariate Cox proportional hazard analyses. CONCLUSION TCBI, a novel and easy to calculate nutrition index, is a useful prognostic indicator in patients with CAD.

Mean platelet volume and long-term cardiovascular outcomes in patients with stable coronary artery disease

BACKGROUND AND AIMS Although an elevated mean platelet volume (MPV) has been associated with poor clinical outcomes after acute coronary syndrome (ACS), the association between MPV and long-term outcomes in patients with stable coronary artery disease (CAD) remains uncertain. We aimed to investigate the impact of pre-procedural MPV levels in patients following elective percutaneous coronary intervention (PCI). METHODS We studied 2872 stable CAD patients who underwent their first PCI and who had available data on pre-procedural MPV between 2002 and 2016. Patients were divided into quartiles based on their MPV. The incidences of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, were evaluated. RESULTS The median MPV was 10.4 fL (interquartile range: 9.8-11.0). During a median follow-up of 5.6 years, 498 (17.3%) MACE were identified, with a cumulative incidence significantly higher in the lowest MPV group than in other groups (p < 0.01). After adjustment for platelet count and the other cardiovascular risk factors, the lowest MPV group had a significantly higher risk of MACE compared with the highest MPV groups (hazard ratio: 1.43, 95% confidence interval 1.10-1.86, p = 0.009). Decreasing MPV as a continuous variable was associated with the incidence of MACE (hazard ratio: 1.16 per 1 fL decrease, 95% confidence interval 1.04-1.30, p = 0.007). CONCLUSIONS Contrary to previous studies on ACS patients, this study showed that a low MPV was associated with worse clinical outcomes among stable CAD patients.